DESCRIPTION: (Applicant's Description) Recent studies suggest that a woman's bone mineral density (BMD) is directly correlated with her risk of breast cancer. Other studies suggest a link between endogenous hormones with both BMD and risk of breast cancer. To date, no studies have examined these factors together in an effort to clarify the independence of these effects and the nature of a possible causal pathway. In this proposal the investigators seek to extend previous research by evaluating these associations in an independent study population and by determining the interelationships between BMD, hormone levels, and breast cancer. The study population consists of 8076 postmenopausal women who were screened at four of the eleven sites from the Fracture Intervention Trial, a randomized clinical trial examining the efficacy of alendronate in the secondary prevention of fractures. In these 8076 women they expect 131 incident breast cancer cases during 4 years of followup. They propose to conduct: (1) a retrospective cohort study to assess increasing BMD as a predictor of risk of breast cancer; (2) a nested case-control study to examine whether increasing levels of free estradiol, estradiol bound to albumin, and total estradiol, and lower levels of estradiol bound to sex hormone binding globulin (SHBG), and SHBG, are associated with an increase in breast cancer risk; (3) a nested case-control analysis to examine if any positive association between BMD and breast cancer is mediated by hormone levels; and (4) a retrospective cohort analysis to assess the relationship between breast cancer risk and factors known to influence BMD (dietary intake of vitamin D, fluoride, and calcium; calcium supplementation; exercise; and weight). Evidence demonstrating the association between BMD and breast cancer is limited but suggestive; however, no studies to date have incorporated the measurement of endogenous estradiol to examine if this association is independent of hormonal status. The investigators will examine the relationship between BMD and breast cancer risk independent of endogenous estradiol as well as examine their contribution together. If BMD predicts breast cancer risk in this cohort, beyond a woman's hormone levels, they will examine other factors that affect BMD, and could therefore also influence risk of breast cancer. In this way, they may be able to identify other pathways involved in the etiology of breast cancer. Identification of a common pathway linking two of the most common health conditions of women, osteoporosis and breast cancer, will have very important implications for understanding the etiology and subsequent prevention of both.